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Eliminating hepatitis B virus as a global health threat

In The Lancet Infectious Diseases, Shevanthi Nayagam mother-to-child transmission, which is the primary
and colleagues1 report a modelling study on the route of transmission in endemic areas. Even with
eectiveness of dierent interventions on the incidence vaccination or hepatitis B immunoglobulin at birth,

Ben Curtis/AP/Press Association Images

and mortality rate of chronic hepatitis B virus (HBV) women with very high viral loads might still transmit
infection. To appreciate the implications of this HBV to their children,5 and the use of antivirals during
report, we need to understand the context. Chronic late pregnancy has been shown to almost eliminate
viral hepatitis is the seventh leading cause of death mother-to-child transmission in this situation.6,7 In
worldwide.2 Chronic HBV infection alone aects over Nayagam and colleagues model,1 peripartum antivirals
240 million people worldwide and is one of the most can further prevent 06 million new cases. Further
common causes of cirrhosis and liver cancer.3 In May, studies are needed to dene the long-term safety of Lancet Infect Dis 2016

2014, the World Health Assembly requested WHO peripartum antivirals in mothers and children. Based Published Online
September 13, 2016
to provide the necessary technical support to enable on these data, low-income countries should prioritise
member states to develop robust national viral hepatitis birth-dose vaccination over peripartum antivirals if they S1473-3099(16)30214-6
See Online/Articles
prevention, diagnosis, and treatment strategies. In do not have the resources to implement both strategies
response, WHO set ambitious goals of reducing new at the same time because the birth-dose vaccination will S1473-3099(16)30204-3
cases of chronic viral hepatitis by 90%, and reducing have a bigger impact than peripartum antivirals.
mortality rates from these infections by 65% between Because most cases of cirrhosis and liver cancer
2015 and 2030.4 Achievement of these goals might at occur during or after middle age, prevention of new
least eliminate chronic viral hepatitis as a major global infections will not have a major eect on HBV-related
health threat. What can we do to make this happen? mortality rates until decades later. Management of
Nayagam and colleagues1 rst assessed the situation patients who have already been infected is, therefore,
at present and compared it with a hypothetical situation important. Although only one placebo-controlled trial
where no intervention had previously been used to has used clinical outcomes as the primary endpoint,8
combat HBV.1 It is gratifying to note that current several observational studies suggest that antivirals
interventions have already had a huge impact: averting can reduce the risk of liver cancer and mortality.9 The
210 million new chronic HBV infections by 2015 and main drawback of antiviral therapy is that long-term
11 million deaths between 2015 and 2030. Nonetheless, treatment is often needed, but drug resistance and
63 million new cases and 17 million HBV-related deaths side eects are rare with entecavir or tenofovir, which
will still occur between 2015 and 2030. The authors then makes long-term treatment acceptable.10 Based on
evaluated ve strategies, including scaling-up infant the estimations in Nayagam and colleagues study,
vaccination coverage to 90%, birth-dose vaccination providing antivirals to 80% of patients with treatment
coverage to 80%, peripartum antivirals coverage for indications can meet the goal of reducing HBV-
mothers with positive hepatitis B e antigen to 80%, related mortality rate by 65% by 2030. Conversely,
increasing access to antivirals to 80%, and developing development of a cure for chronic hepatitis B would not
a cure for HBV infection. The rst three interventions have an additional eect on mortality rate. This is hardly
target new infections, whereas HBV treatments prevent surprising because the authors assume that adequate
disease progression, cirrhotic complications, and liver HBV suppression by available antivirals is as eective
cancer. as curing HBV. However, antivirals reduce, but do not
Compared with the present state, scaling-up infant eliminate, the risk of liver cancer,11 so the eect of curing
vaccination can prevent 43 million new infections HBV should be revisited when such a drug becomes
from 2015 to 2030, but the real impact comes from available.
birth-dose vaccination, which prevented 187 million We commend the authors for extensively reviewing
new cases of HBV infection. The smaller eect of infant data from dierent regions and providing information
vaccination compared with birth-dose vaccination that is urgently needed.1 But knowing the eectiveness
is because infant vaccination is ineective against of the strategies is only the rst step. The benets Published online September 13, 2016 1


will not materialise if the interventions are not GL-HW has served as an advisory board member for Gilead and has received paid
lecture fees from AbbVie, Bristol-Myers Squibb, Echosens, Gilead, Janssen, and
implemented. Some policies that sound straightforward Roche. VW-SW has served as an advisory board member for Gilead and Janssen;
in the developed world can face major hurdles in low- as a consultant for AbbVie, Merck, and NovoMedica; and has received paid
lecture fees from AbbVie, Echosens, Gilead, Merck, and Roche.
income and middle-income countries. For example,
Copyright The Author(s). Published by Elsevier Ltd. This is an Open Access
the transportation of vaccines to remote areas and article under the CC BY license
temperature control can already be a challenge, not 1 Nayagam S, Thursz M, Sicuri E, et al. Requirements for global elimination
to mention the need to train health-care providers of hepatitis B: a modelling study. Lancet Infect Dis 2016; published online
Sept 13.
and educate the public. Patient management would 2 WHO. Viral hepatitis. Sept 11, 2015.
not be possible without access to diagnostic tests (accessed June 23, 2016).
and monitoring instruments. Safe needles and blood 3 Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of
worldwide prevalence of chronic hepatitis B virus infection: a systematic
products should be available to all countries. Finally, these review of data published between 1965 and 2013. Lancet 2015;
programmes cannot be sustained without adequate 386: 154655.
4 WHO. Draft global health sector strategies. Viral hepatitis, 20162021.
funding. According to Nayagam and colleagues forecast, April 22, 2016.
the annual expenditure between 2015 and 2030 needed en.pdf?ua=1 (accessed June 23, 2016).
5 Wen WH, Chang MH, Zhao LL, et al. Mother-to-infant transmission of
to achieve the goals will be US$55 billion. Although this hepatitis B virus infection: signicance of maternal viral load and strategies
for intervention. J Hepatol 2013; 59: 2430.
will be a good investment because cirrhosis and liver
6. Chen HL, Lee CN, Chang CH, et al. Ecacy of maternal tenofovir disoproxil
cancer could be avoided, governments still need to nd fumarate in interrupting mother-to-infant transmission of hepatitis B
virus. Hepatology 2015; 62: 37586.
ways to nance these programmes. 7 Pan CQ, Duan Z, Dai E, et al. Tenofovir to prevent hepatitis B transmission
With determination, the WHO 2030 goals for in mothers with high viral load. N Engl J Med 2016; 374: 232434.
8 Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic
chronic viral hepatitis can be and should be achieved. hepatitis B and advanced liver disease. N Engl J Med 2004; 351: 152131.
Achievement of this goal calls for concerted eort from 9 Wong GL, Chan HL, Mak CW, et al. Entecavir treatment reduces hepatic
events and deaths in chronic hepatitis B patients with liver cirrhosis.
policy makers, clinicians, and societies. The tools to Hepatology 2013; 58: 153747.
combat HBV are already at hand, and now is the time for 10 Wong GL, Tse YK, Wong VW, Yip TC, Tsoi KK, Chan HL. Long-term safety of
oral nucleos(t)ide analogs for patients with chronic hepatitis B: a cohort
action. study of 53,500 subjects. Hepatology 2015; 62: 68493.
11 Wong GL, Chan HL, Chan HY, et al. Accuracy of risk scores for patients with
chronic hepatitis B receiving entecavir treatment. Gastroenterology 2013;
Grace Lai-Hung Wong, *Vincent Wai-Sun Wong 144: 93344.
Department of Medicine and Therapeutics, and State Key Laboratory
of Digestive Disease, The Chinese University of Hong Kong, Shatin,
Hong Kong Special Administrative Region, China

2 Published online September 13, 2016